scholarly journals Large Animal Models of Huntington’s Disease: What We Have Learned and Where We Need to Go Next

2020 ◽  
Vol 9 (3) ◽  
pp. 201-216
Author(s):  
David Howland ◽  
Zdenka Ellederova ◽  
Neil Aronin ◽  
Deborah Fernau ◽  
Jill Gallagher ◽  
...  
Keyword(s):  
Animal Models ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Single Species ◽  
Research Community ◽  
Response To Treatment ◽  
Large Animal ◽  
Rodent Models ◽  
Large Animal Models ◽  
Translational Studies

Genetically modified rodent models of Huntington’s disease (HD) have been especially valuable to our understanding of HD pathology and the mechanisms by which the mutant HTT gene alters physiology. However, due to inherent differences in genetics, neuroanatomy, neurocircuitry and neurophysiology, animal models do not always faithfully or fully recapitulate human disease features or adequately predict a clinical response to treatment. Therefore, conducting translational studies of candidate HD therapeutics only in a single species (i.e. mouse disease models) may not be sufficient. Large animal models of HD have been shown to be valuable to the HD research community and the expectation is that the need for translational studies that span rodent and large animal models will grow. Here, we review the large animal models of HD that have been created to date, with specific commentary on differences between the models, the strengths and disadvantages of each, and how we can advance useful models to study disease pathophysiology, biomarker development and evaluation of promising therapeutics.

scholarly journals Characterisation of the horse transcriptome from immunologically active tissues

2014 ◽  
Author(s):  
Joanna Moreton ◽  
Sunir Malla ◽  
Aziz Aboobaker ◽  
Rachael Tarlinton ◽  
Richard D Emes
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Animal Models ◽  
Genome Annotation ◽  
Large Animal ◽  
Suitable Model ◽  
Rodent Models ◽  
Large Animal Models ◽  
Human Disorders ◽  
Novel Isoforms

The immune system of the horse has not been well studied, despite the fact that the horse displays several features such as sensitivity to bacterial lipopolysaccharide that make them in many ways a more suitable model of some human disorders than the current rodent models. The difficulty of working with large animal models has however limited characterisation of gene expression in the horse immune system with current annotations for the equine genome restricted to predictions from other mammals and the few described horse proteins. This paper outlines sequencing of 184 million transcriptome short reads from immunologically active tissues of three horses including the genome reference “Twilight”. In a comparison with the Ensembl horse genome annotation, we found 8,763 potentially novel isoforms.

Synaptic Dysfunction in Huntington’s Disease: Lessons from Genetic Animal Models

2020 ◽  
pp. 107385842097266
Author(s):  
Carlos Cepeda ◽  
Michael S. Levine
Keyword(s):  
Basal Ganglia ◽  
Animal Models ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Structural Changes ◽  
Synaptic Proteins ◽  
Synaptic Dysfunction ◽  
Rodent Models ◽  
Cell Degeneration ◽  
Late Stages

The understanding of the functional and structural changes occurring in the cerebral cortex and basal ganglia in Huntington’s disease (HD) has benefited considerably from the generation of genetic animal models. Most studies of synaptic alterations in HD models have focused on the striatum, but a more complete picture of synaptic dysfunction in the cortico-basal ganglia-cortical loop is emerging. Here, we provide a review and analysis of current developments in the study of synaptic alterations in these areas using HD rodent models. Recent evidence indicates that cortical maldevelopment plays a role in synaptic dysfunction along the corticostriatal pathway that may have its roots in the way mutant huntingtin interacts with synaptic proteins. Furthermore, a progressive disconnection in the corticostriatal pathway leads to abnormal function engaging extrasynaptic N-methyl-D-aspartate glutamate receptors that contribute to eventual cell degeneration. In addition, biphasic increases followed by decreases in glutamate and dopamine release in the striatum could explain contrasting symptomatology in early and late stages of the disease. Changes in striatal output regions also are beginning to be examined. Finally, we highlight some therapeutic avenues aimed at rescuing synaptic dysfunction.

scholarly journals Porcine Models of Accelerated Coronary Atherosclerosis: Role of Diabetes Mellitus and Hypercholesterolemia

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Damir Hamamdzic ◽  
Robert L. Wilensky
Keyword(s):  
Animal Models ◽  
Coronary Atherosclerosis ◽  
Pig Model ◽  
Large Animal ◽  
Rodent Models ◽  
Miniature Pig ◽  
Therapeutic Approaches ◽  
Large Animal Models ◽  
Atherosclerotic Lesions

Animal models of atherosclerosis have proven to be an invaluable asset in understanding the pathogenesis of the disease. However, large animal models may be needed in order to assess novel therapeutic approaches to the treatment of atherosclerosis. Porcine models of coronary and peripheral atherosclerosis offer several advantages over rodent models, including similar anatomical size to humans, as well as genetic expression and development of high-risk atherosclerotic lesions which are similar to humans. Here we review the four models of porcine atherosclerosis, including the diabetic/hypercholesterolemic model, Rapacz-familial hypercholesterolemia pig, the (PCSK9) gain-of-function mutant pig model, and the Ossabaw miniature pig model of metabolic syndrome. All four models reliably represent features of human vascular disease.

scholarly journals Characterisation of the horse transcriptome from immunologically active tissues

2014 ◽  
Author(s):  
Joanna Moreton ◽  
Sunir Malla ◽  
Aziz Aboobaker ◽  
Rachael Tarlinton ◽  
Richard D Emes
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Animal Models ◽  
Genome Annotation ◽  
Large Animal ◽  
Suitable Model ◽  
Rodent Models ◽  
Large Animal Models ◽  
Human Disorders ◽  
Novel Isoforms

The immune system of the horse has not been well studied, despite the fact that the horse displays several features such as sensitivity to bacterial lipopolysaccharide that make them in many ways a more suitable model of some human disorders than the current rodent models. The difficulty of working with large animal models has however limited characterisation of gene expression in the horse immune system with current annotations for the equine genome restricted to predictions from other mammals and the few described horse proteins. This paper outlines sequencing of 184 million transcriptome short reads from immunologically active tissues of three horses including the genome reference “Twilight”. In a comparison with the Ensembl horse genome annotation, we found 8,763 potentially novel isoforms.

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